Epilepsy affects approximately 50 million of people worldwide and 30% of them are resistant to drugs. Neuromodulation is becoming a key option in patients with drug-resistant epilepsy who are not feasible for resective surgery. Vagus nerve stimulation (VNS) is the most commonly used adjunctive neuromodulatory method in every patient aged 4 years and older who is unsuitable for resective surgery. It is a minimally invasive, non-teratogenic, extracranial pacemaker-like device which delivers electrical stimuli to the vagus nerve and desynchronize aberrant cerebral rhythms involved in epileptogenesis. In this review we approached the information and clinical data of VNS development history, clinical applications and possible mechanism of action. We will also review optimal stimulation parameters and information about closed and open loop devices. Vagus nerve stimulation is safe, efficient with no significant side effects and substantial cost-saving benefit, that also shows an important improvement in mood, behavior, cognition and quality of life. The overall responder rate was observed in more than 50% of patients. On the other hand, it is not clear which patients will respond to this method of treatment and why the response is not immediate, there are no available biomarkers or other features like age, sex, seizure type/epileptic syndrome to predict response to vagus nerve stimulation therapy. The VNS Therapy System continues to be an important prospect in the treatment of pharmacoresistant epilepsy, that requires further studies in order to ensure the most advantageous therapeutic response.
Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modified Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed.
Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZ-kindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg).
Results: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported.
Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.
One of the most frequent forms of epilepsy in humans is temporal lobe epilepsy. Characteristic to this form of the disease is the frequent pharmacoresistance and the association with behavioural disorders and cognitive impairment. The objective of our study was to establish the degree of cognitive impairment in a rat model of temporal lobe epilepsy after an initial epileptogenic exposure but before of the onset of the effect of long-duration epilepsy.
Methods. For the experiment we used 11 rats. Status epilepticus was induced by systemic administration of a single dose of pilocarpine. The animals were continuously video-monitored to observe the occurrence of spontaneous recurrent seizures; during weeks 9-10 we performed eight-arm radial maze testing in order to assess the cognitive impairment.
Results. Animals developed spontaneous recurrent seizures after a 14-21 day latency with a daily average seizure density of 0.79±0.43 during weeks 9-10. Epileptic rats had significantly more working memory errors per session, more reference memory errors and the number of visited arms was also significantly higher. Accuracy was also lower in the pilocarpine treated group. Interestingly significant differences disappeared after six days of trials.
Conclusions. Our study shows behavioural deficits occurring after 9-10 weeks of epilepsy in the pilocarpine model of epilepsy applied to juvenile rats. In contrast to previous studies, we showed that juvenile rats with short duration of epilepsy are able to learn the behavioural task, therefore a morphopathological and/or behavioural “no-return point” regarding the development of severe cognitive impairment is not reached by status epilepticus alone.
Objectives: the aim of the study was to identify predictive risk factors of the development of epilepsy in patients with cerebral palsy (CP).
Materials and methods: We performed a bidirectional study in wich 177 patients diagnosed with CP with and without epilepsy have been selected for characteristics and risk factor comparison. We analyzed the history related to pregnancy and birth, gestational age, birth weight, fetal distress, the presence of neonatal convulsion, age of onset for the epilepsy, associated types of seizures, the response to anticonvulsant therapy and brain changes identified by Computer tomography and Magnetic resonance imaging examination.
Results: epilepsy was found in 91 (51.4%) patients, most frequently in quadriplegic form (76.2% vs 23.8%), OR:3.04, 95% CI:1.42-6.52, p-0.005. In this group, the most common were partial seizures (34.4%), epileptic encephalopathy like Lennox Gastaut and West type (62.5%), and also neonatal seizures. Eighty percent of on-term infants with neonatal seizures later developed epilepsy. Factors like fetal distress, low birth weight, cytomegalovirus infection, history of pathological pregnancy were associated with an increased risk of developing epilepsy. Imaging change, especially cerebral atrophy had the highest frequency (37.5% vs 16%) in pacients with epilepsy. 28 (30.8%) patients had resistance epilepsy, 13 (46.4%) of them having quadriplegia. Early onset of epilepsy constitutes a sign of severity of epileptic forms (OR:3.09, 95% CI:1.187-8.061, p-0.01).
Conclusions: The data are consistent with those in literature but is necessary following this study to clarify and support the assumption on preddictive factors and prognosis of epilepsy in this population.